Potent antitumor effect elicited by gp96-peptide complexes pulsed by dendritic cell on mice of H22 liver cancer

Objective: To improve DC-based tumor vaccination, we studied whether dendritic cells (DCs) which cocultured with H22 liver cancer cells-derived heat shock protein (HSP) glycoprotein 96 (gp96) affect the T cell-activating potential in vitro and the induction of tumor immunity in vivo. Methods: Maturation of murine bone marrow-derived DC was induced by GM-CSF plus IL-4. which mimiced the immunostimulatory effect of DC. Cocultured DC and gp96-peptide complexes were used to vaccine H22 liver cancer cells of mice. Using murine models we compared the immunogenecity of DC modified by gp96-peptides complexes derived from murine liver cancer cells alone or inactive tumor cells. To verify the specificity of the vaccine, in vitro assays were executed. Serum cytokine levels were quantified to explore the supposed pathway of DC modified by gp96 peptide complexes and its effect on antitumor immune response. Results: DC modified by gp96-peptide complexes can activate spleen lymphocyte and the latter can specifically kill H22 cells but not Ehrilich ascites carcinoma cells. Modified DC can induce potent tumor-antigenspecific immune response, augment the proliferation of Th1 cells, and inhibit tumor growth. Conclusion: In this study, we have developed a novel DC-mediated tumor vaccine by combing the gp96 antigenic peptides complexes and inducing immune response against specific tumor cells. gp96 can be identified as a potent DC activator.

Objective： To improve DC-based tumor vaccination, we studied whether dendritic ceils （DCs） which cocultured with H22 liver cancer cells-derived heat shock protein （HSP） glycoprotein 96 （gp96） affect the T cell-activating potential in vitro and the induction of tumor immunity in vivo. Methods： Maturation of murine bone marrow-derived DC was induced by GM-CSF plus IL-4, which mimiced the immunostimulatory effect of DC. Cocultured DC and gp96-peptide complexes were used to vaccine H22 liver cancer cells of mice. Using murine models we compared the immunogenecity of DC modified by gp96-peptides complexes derived from murine liver cancer cells alone or inactive tumor cells. To verify the specificity of the vaccine, in vitro assays were executed. Serum cytokine levels were quantified to explore the supposed pathway of DC modified by gp96 peptide complexes and its effect on antitumor immune response. Results： DC modified by gp96-peptide complexes can activate spleen lymphocyte and the latter can specifically kill H22 cells but not Ehrilich ascites carcinoma cells. Modified DC can induce potent tumor-antigenspecific immune response, augment the proliferation of Thl cells, and inhibit tumor growth. Conclusion： In this study, we have developed a novel DC-mediated tumor vaccine by combing the gp96 antigenic peptides complexes and inducing immune response against specific tumor cells, gp96 can be identified as a potent DC activator.